PMID- 29783074 OWN - NLM STAT- MEDLINE DCOM- 20180613 LR - 20180613 IS - 1879-0038 (Electronic) IS - 0378-1119 (Linking) VI - 668 DP - 2018 Aug 20 TI - FSH receptor binding inhibitor restrains follicular development and possibly attenuates carcinogenesis of ovarian cancer through down-regulating expression levels of FSHR and ERbeta in normal ovarian tissues. PG - 174-181 LID - S0378-1119(18)30563-8 [pii] LID - 10.1016/j.gene.2018.05.068 [doi] AB - OBJECTIVES: The current study aimed to investigate FSH receptor binding inhibitor (FRBI) effects in the expressions of FSH receptor (FSHR) and estrogen receptor-beta (ERbeta) in the mice ovaries at the gene and protein levels, also to find the potential efficacy of FRBI on suppressing ovarian cancer through down-regulating over-expression of FSHR and ERbeta in the normal ovarian tissues. METHODS: 180 female mice were randomized into six groups (n = 30). Mice of FRBI-1, FRBI-2 and FRBI-3, FRBI-4 were intramuscularly injected with FRBI of 10, 20, 30 and 40 mg/kg, respectively, for five consecutive days. The qPCR and Western blotting were used to determine expression levels of FSHR and ERbeta mRNAs and proteins in mouse ovaries. RESULTS: The ovarian cortex thickness (OCT) of the FRBI-4 group were less than that FSH group on day 30 (P < 0.05). The numbers of secondary follicles (SF) and the maximum transverse diameters (MTD) of secondary follicles of FRBI-3 and FRBI-4 groups were decreased as compared to FSH group (P < 0.05 or P < 0.01) by 24.11% and 27.47% on day 20 based on the control group (CG) levels. On day 15, the reductions of FSHR mRNA levels in FRBI-2, FRBI-3 and FRBI-4 were 27.78%, 29.37% and 43.65% (P < 0.05 or P < 0.01), respectively in comparison with CG. ERbeta and FSHR protein levels of FRBI-treated mice were gradually decreased as compared to and CG and FSH group. ERbeta protein level of FRBI-4 was less than that of CG on day 20 (P < 0.05). On days 15 and 20, estradiol (E(2)) concentrations of FRBI-2, FRBI-3 and FRBI-4 groups were lower than those of the CG and FSH group (P < 0.05 or P < 0.01). CONCLUSIONS: FRBI could reduce OCT and follicle numbers. A high dose of FRBI (30 mg/kg to 40 mg/kg) could suppress ovarian and follicular development, and attenuate expression levels of ERbeta and FSHR mRNAs and proteins in the ovaries, additionally inhibit E(2) production. Therefore, FRBI will possibly be utilized to restrain the carcinogenesis of ovarian cancer by down-regulating overexpression of FSHR and ERbeta in the ovaries. CI - Copyright (c) 2018 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Zhuandi, Gong AU - Zhuandi G AD - Hospital of Medicine College, Northwest Minzu University, China. FAU - Tuanjie, Che AU - Tuanjie C AD - Key Laboratory of Functional Genomic and Molecular Diagnosis of Gansu Province, China. FAU - Luju, Lai AU - Luju L AD - Life Science and Engineering College, Northwest Minzu University, China. FAU - Abdiryim, Ayimuguli AU - Abdiryim A AD - Life Science and Engineering College, Northwest Minzu University, China. FAU - Yingying, Deng AU - Yingying D AD - Research Center of Animal Cell Engineering and Technology of Gansu Province, Northwest Minzu University, China. FAU - Haoqin, Liang AU - Haoqin L AD - Life Science and Engineering College, Northwest Minzu University, China. FAU - Suocheng, Wei AU - Suocheng W AD - Life Science and Engineering College, Northwest Minzu University, China; Research Center of Animal Cell Engineering and Technology of Gansu Province, Northwest Minzu University, China. Electronic address: weisc668@163.com. FAU - Li, Ding AU - Li D AD - Technology Center of Hunan Entry-exit Inspection and Quarantine Bureau, China. Electronic address: dingli0824@126.com. LA - eng PT - Journal Article DEP - 20180518 PL - Netherlands TA - Gene JT - Gene JID - 7706761 RN - 0 (Estrogen Receptor beta) RN - 0 (Peptides) RN - 0 (RNA, Messenger) RN - 0 (Receptors, FSH) RN - 4TI98Z838E (Estradiol) SB - IM MH - Animals MH - Carcinogenesis MH - Down-Regulation MH - Estradiol/blood MH - Estrogen Receptor beta/*metabolism MH - Female MH - Gene Expression MH - Mice MH - Ovarian Follicle/anatomy & histology/drug effects MH - Ovarian Neoplasms/etiology MH - Ovary/anatomy & histology/drug effects/*metabolism MH - Peptides/pharmacology MH - RNA, Messenger/metabolism MH - Receptors, FSH/genetics/*metabolism OTO - NOTNLM OT - Estrogen receptor OT - FSH receptor binding inhibitor OT - Follicle stimulating hormone OT - Mice OT - Ovarian cancer OT - Overexpression EDAT- 2018/05/22 06:00 MHDA- 2018/06/14 06:00 CRDT- 2018/05/22 06:00 PHST- 2018/03/09 00:00 [received] PHST- 2018/05/08 00:00 [revised] PHST- 2018/05/17 00:00 [accepted] PHST- 2018/05/22 06:00 [pubmed] PHST- 2018/06/14 06:00 [medline] PHST- 2018/05/22 06:00 [entrez] AID - S0378-1119(18)30563-8 [pii] AID - 10.1016/j.gene.2018.05.068 [doi] PST - ppublish SO - Gene. 2018 Aug 20;668:174-181. doi: 10.1016/j.gene.2018.05.068. Epub 2018 May 18.